%0 Journal Article %J J Psychiatr Res %D 2021 %T Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders. %A Sreeraj, Vanteemar S %A Puzhakkal, Joan C %A Holla, Bharath %A Nadella, Ravi Kumar %A Sheth, Sweta %A Balachander, Srinivas %A Ithal, Dhruva %A Ali, Furkhan %A Viswanath, Biju %A Muralidharan, Kesavan %A Venkatasubramanian, Ganesan %A John, John P %A Benegal, Vivek %A Murthy, Pratima %A Varghese, Mathew %A Reddy, Yc Janardhan %A Jain, Sanjeev %X

BACKGROUND: Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia).

METHODS: Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).

RESULTS: MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.

CONCLUSION: MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.

%B J Psychiatr Res %V 142 %P 54-62 %8 2021 Jul 20 %G eng %R 10.1016/j.jpsychires.2021.07.028 %0 Journal Article %J Aust N Z J Psychiatry %D 2020 %T Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses. %A Someshwar, Amala %A Holla, Bharath %A Pansari Agarwal, Preeti %A Thomas, Anza %A Jose, Anand %A Joseph, Boban %A Raju, Birudu %A Karle, Hariprasad %A Muthukumaran, M %A Kodancha, Prabhath G %A Kumar, Pramod %A Reddy, Preethi V %A Kumar Nadella, Ravi %A Naik, Sanjay T %A Mitra, Sayantanava %A Mallappagiri, Sreenivasulu %A Sreeraj, Vanteemar S %A Balachander, Srinivas %A Ganesh, Suhas %A Murthy, Pratima %A Benegal, Vivek %A Reddy, Janardhan Yc %A Jain, Sanjeev %A Mahadevan, Jayant %A Viswanath, Biju %X

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study.

METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder ( = 61), obsessive-compulsive disorder ( = 58), schizophrenia ( = 52), substance dependence ( = 59) or co-occurring diagnoses ( = 38), while 241 were at-risk first-degree relatives who were either unaffected ( = 210) or had other depressive or anxiety disorders ( = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated.

RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder.

CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

%B Aust N Z J Psychiatry %V 54 %P 1086-1094 %8 2020 Nov %G eng %N 11 %R 10.1177/0004867420931157 %0 Journal Article %J BMC Psychiatry %D 2018 %T Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science. %A Viswanath, Biju %A Rao, Naren P %A Narayanaswamy, Janardhanan C %A Sivakumar, Palanimuthu T %A Kandasamy, Arun %A Kesavan, Muralidharan %A Mehta, Urvakhsh Meherwan %A Venkatasubramanian, Ganesan %A John, John P %A Mukherjee, Odity %A Purushottam, Meera %A Kannan, Ramakrishnan %A Mehta, Bhupesh %A Kandavel, Thennarasu %A Binukumar, B %A Saini, Jitender %A Jayarajan, Deepak %A Shyamsundar, A %A Moirangthem, Sydney %A Vijay Kumar, K G %A Thirthalli, Jagadisha %A Chandra, Prabha S %A Gangadhar, Bangalore N %A Murthy, Pratima %A Panicker, Mitradas M %A Bhalla, Upinder S %A Chattarji, Sumantra %A Benegal, Vivek %A Varghese, Mathew %A Reddy, Janardhan Y C %A Raghu, Padinjat %A Rao, Mahendra %A Jain, Sanjeev %X

BACKGROUND: There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository.

METHODS: The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing.

DISCUSSION: We hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

%B BMC Psychiatry %V 18 %P 106 %8 2018 Apr 18 %G eng %N 1 %R 10.1186/s12888-018-1674-2